חוות דעת ייצוגית declan waugh

8/13/2019 Declan Waugh

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14th January 2014

This information is submitted on behalf of the people of Israel to Tel Aviv DistrictCourt upon the request of the lawyer Dan Ashkenazi and the lawyer Dikla Baranes,the representatives of the petitioner (Jacob Gurman).This document addresses some of the critical toxicological and human health risksassociated with artificial fluoridation of public water. As you are aware the challengesfaced by the State and the citizens of your country to the soaring rise in the burden ofchronic disease are unprecedented. The number of patients presenting with chronicdiseases including arthritis, heart disease, respiratory problem, cancer, mental healthconditions such as depression and dementia as well as metabolic diseases such asobesity, diabetes have risen dramatically in recent years. While this has occurred forvarious reasons, it is clear however that public health authorities in certain countrieswhere artificial fluoridation is practiced continue to live in a state of denial as to theincreasing evidence of the role of fluoride exposure to chronic disease burdens; particularly where these disease burdens are significantly above the norm and wherethere is an established documented role in the contribution of fluoride in the pathogenesis of these diseases. It is evident that national authorities either lack thecapacity or are unwilling to examine the published scientific facts that clearlydemonstrate how artificial fluoridation of their populations is a serious threat to publichealth. This document aims to identify the key issues and major risk factorsassociated with artificial fluoridation that ultimately may significantly reduce the riskof chronic illness from exposure to highly soluble inorganic fluorides.

When examining the published scientific evidence a number of facts are beyonddispute. This letter and supporting documentation aims to set the record straight abouta number of indisputable facts, the foremost of which is that the fluoride ion is a pro-inflammatory agent and that exposure to fluoride increases free radical production andoxidative stress in humans. Inflammation forms the basis of many physiological and pathological processes. Chronic and low grade inflammation forms the basis of manyhuman diseases ranging from type 2 diabetes and depression to heart disease, manyforms of cancer, as well as many neurological diseases. Atherosclerosis provides anexample of a chronic disease that involves inflammatory mechanisms and fluoride has been demonstrated to have a causal role in atherosclerosis. Fluoride is recognized as alow dose endocrine disrupting substance that can alter the normal endocrine function

at dietary intake concentrations significantly below the typical dietary intake levels present in fluoridated communities. It is also acknowledged that fluoride disruptscellular calcium and magnesium homeostatis and is a potent enzymatic and metabolicinhibitor. Research has demonstrated that fluoride is a risk factor in cardiovasculardisease, as well as other major diseases including inflammatory respiratory diseaseand metabolic diseases such as diabetes and obesity. Fluoride is also now recognisedas a neurotoxin that may contribute to reduced IQ and neurodegenerative disorderssuch as Alzheimers. Recent research has also documented that fluoride inhibits theimmune system increasing susceptible to biochemical injury from other toxins.Fluoride is also a bioaccumulative toxin, once ingested it accumulates in the bodyover time, therefore as people live longer the level of environmental contamination in

the human body increases. People with higher levels have a greater risk of chronichealth problems.


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It is an irrefutable fact that in countries that implement artificial fluoridation policiesthat infants and adults are chronically exposed to fluoride at levels that are detrimentalto their health and general wellbeing. The failure of the State to so far recognise thisfact is deeply worrying especially when chronic overexposure of infants wasidentified by a scientific committee of the European Food Safety Authority in 2006.The report also addresses the chronic overexposure of the adult population tofluorides discussing in particular the recent published study by Chan et al., (2013) ondietary fluoride exposure of the UK population which found that a significant percentage of the adult population were chronically exposed to fluoride at levels thatwere detrimental to their health and general wellbeing from the consumption of tea,without exposure to fluoridated water or foodstuffs. Importantly, their findings onfluoride concentrations in tea are in agreement with all published data reported byresearchers globally.

I have included in the appendix a detailed report, which while only addressingspecific scientific areas of concern, nevertheless incorporates the published scientificevidence from peer reviewed publications to demonstrate how artificial fluoridation iscontributing to chronic overexposure of the population, particularly infants, whorepresent the most sensitive subgroup. The report documents the published scientificstudies which demonstrate how fluoride exposure is contributing to chronic disease.The following twenty one points summarises some of the key facts. Each of thesestatements are irrefutable facts and scientific references are provided in the appendix.

Indisputable facts:

1. In countries that practice artificial fluoridation of public water bottle fedinfants are chronically overexposed to fluoride at levels that are detrimental totheir health and wellbeing.

2. Chronic overexposure to fluoride also exists in the adult population in bothfluoridated and non-fluoridated countries from consumption of tea. Theexposure increases when tea is constituted with fluoridated water.

3. Fluoride is a pro-inflammatory agent which increases the inflammatoryresponse in humans. Chronic and low grade inflammation forms the basis ofmany human diseases ranging from type 2 diabetes and depression to heart

disease, endocrine disorders, metabolic diseases, respiratory andmusculoskeletal disease, many forms of cancer, and neurological diseasessuch as dementia.

4. Increasing proinflammatory status is a recognised causal factor in developinghyperglycemia and insulin resistance. Maternal hyperglycemia has a causalrelationship with increasing fetal growth and pregnancy complicationsincluding cesarean section, in addition to contributing to increased childhoodobesity. Fluoride inhibits normal carbohydrate metabolism, resulting in anaccumulation of fatty acids and an increased risk of obesity and diabetes. TheRoI has the highest prevalence of childhood obesity in the EU and 24% of

adults are classified as obese. The top six countries for obesity among OECDmember nations are all countries with artificial fluoridation programmes.


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5. Fluoride alters normal endocrine function. Altered endocrine function isassociated with increased cholesterol concentrations, increased incidence ofdepression, diminished response to standard psychiatric treatment, cognitivedysfunction, and, in pregnant women, decreased IQ of their offspring. Forindividuals with iodine deficiency a total dietary intake of 0.7 3.6mg per dayis known to adversely affect thyroid function, up to 50% of European population are deficient in iodine. The European Food Safety Authority hasestablished that total daily dietary fluoride intakes, excluding medicine andtoothpaste, for individuals living in countries with artificial fluoridation mayexceed 6.5mg per day. Consequently it can be stated with absolute certaintythat artificial fluoridation of public water is contributing to disruption ofhealthy endocrine function and diseases associated with exposures toendocrine disrupting.

6. Fluoride increases the production of free radicals and oxidative stress. Freeradical and oxidative stress are causal factors in cancer. According to theWorld Health organisation (2013) the Republic of Ireland (RoI) has thehighest incidence of cancer in Western Europe almost twice that of the meanincidence of entire European Region. In addition, according to the NationalCancer Registry of Ireland the risk of developing cancers including leukaemia, bladder, prostate, oesophagus, cervix pancreas and brain/central nervoussystem cancers was significantly higher in RoI than in NI, which is non-fluoridated.

7. Fluoride increases the production of calcitonin at dietary intake levels lessthan those reported for individuals living in fluoridated communities.Increased calcitonin levels are associated with coronary artery disease,inflammatory lung disease, major depressive disorders, and migraine and playa pivotal role in the pathogenesis of prostate cancer. Elevated calcitonin is alsoassociated with thyroid cancer, lung, ovarian, pancreatic and breast cancer.The prevalence of depressive disorders, heart disease and cancer in the RoI aresignificantly above the European region and amongst the highest reportedinternationally. The European Medicines Agencys Committee for MedicinalProducts for Human Use (2012) determined that calcitronin increases cancerrisk and have advised that calcitronin medications no longer be prescribed bymedical physicians.

8. Free radicals and oxidative stress are causal factors in neurological diseaseincluding depressive anxiety disorders. It is an established medical fact thatoxidative damage in the brain causes nervous system impairment contributingto schizophrenia, depression, anxiety disorders and high anxiety levels. Irelandhas the highest prevalence of depressive disorders in Europe. In addition,anxiety disorders are also the most common class of psychiatric disorders inthe US, the country with the longest period of artificial fluoridation, affectingapproximately 28.8% of the US population. In stark contrast the EuropeanStudy of the Epidemiology of Mental Disorders (2004) reported a prevalencerate for anxiety disorders among six European countries of 6.8%.


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9. Fluoride has also been demonstrated to directly stimulate activation of G proteins. G proteins have been implicated in the pathophysiology severaldiseases including, inflammation, neurological diseases, cardiovasculardiseases, cancer, and endocrine disorders. Fluoride is documented to causecoronary vasospasms by stimulating G-proteins to release EDRF(endothelium-derived relaxing factor).Vasospasms are known to be a majorrisk factor in ischemia and strokes. The Republic of Ireland has the secondhighest mortality rate from ischaemic heart disease in the Western Europe and premature deaths for individuals below 65 yrs of age from ischaemic heartdisease are above the EU15 and EU27.

10. Free radicals play causal role in pathogenesis of atherosclerosis leading tovascular diseases. Oxidative stress plays a causal role in neurodegenerativediseases such as Parkinsons disease (PD), Alzheimers disease (AD) andMultiple Sclerosis (MS).

11. Fluoride alters Calcium and Magnesium homeostasis with wide rangingimplications for public health including increased risk of osteoporosis, thyroiddisorders, obesity, hypertension and colon cancer. According to the NationalCancer Registry Ireland the incidence of colon cancer in the RoI is higher thanthe European average for both males and females. In 2010, according to theInstitute of Public Health (IPH), more than 950,000 (62.2%) adults aged 45+years in RoI have hypertension and more than 67,000 (3.7%) adults aged 18-44 years in RoI have clinically diagnosed hypertension. By 2020 the IPHreported that the number of adults aged 45+ years with hypertension isexpected to rise by 28% to more than 1,220,000. The differences in prevalencerates in the Island of Ireland are remarkable, with more than 75% of adultsaged 65 years or over in the RoI clinically diagnosed with hypertensioncompared to 48% in non-fluoridated Northern Ireland. Similar regionaldifferences have been reported for prevalence rates of osteoporosis, with prevalence rates in the RoI twice that reported for the UK. In addition, theestimated prevalence of overweight in adults in the RoI is 37%, with 24%documented as obese.

12. Fluoride is a cholinesterase inhibitor. There is a recognised causal relationship between cholinesterase inhibitors and pulmonary disorders including pneumonia, persistent cough, bronchitis, and asthma. Within Europe the RoI

also has the highest prevalence of adult and childhood asthma. Death ratesfrom diseases of the respiratory system in Ireland are almost double the EUaverage and the RoI also has the highest hospitalization of 0-14 yrs. olds forasthma among European counties. The countries with the highest burdens of pulmonary respiratory disease globally, at levels significantly above the globalaverages, are all countries with advanced artificial fluoridation programmes.

13. Fluoride inhibits carbohydrate metabolism through inhibition of key enzymescontributing to increased rates of obesity. As a proinflammatory agent fluoridecontributes to hyperglycemia and insulin resistance. There is an establishedassociation between diminished insulin resistance and hyperglycemia in

pregnancy and childhood obesity. The highest rates of adult obesity amongOECD countries are reported in countries with artificial fluoridation, including


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the U.S.A, New Zealand, Australia and the RoI. Among European countriesthe RoI has the highest prevalence of overweight and obese children in theEuropean region, while the prevalence of overweight in adults is 37%, with afurther 24% meeting current body mass index (BMI) criteria for obesity.

14. Fluoride inhibits enolase. In addition to its innate glycolytic function enolase plays an important role in several biological and pathophysiological processesincluding autoimmune disorders, cardiovascular health, inflammatoryrespiratory disease, cancer, Alzheimer's disease, rheumatoid arthritis,inflammatory bowel disease and general disease prevention.

15. Fluoride impairs glucose tolerance and causes decreased insulin expressionand increased insulin resistance. Glucose intolerance is a gateway todeveloping type 2 diabetes. Incidence rates for diabetes in the RoI aresignificantly above those for Northern Ireland or the European region.

16. Increased insulin resistance and impaired gyycemic control are establishedrisk factors in depressive disorders. The RoI has one of the highest incidencerates for depressive disorders in the world.

17. Fluoride inhibits Lipase. Among individuals with conditions that cancontribute to a lipase deficiency, there is the potential for problems to develop,such as prostate disorders, high cholesterol, an increased risk for diabetes, anddifficulty losing weight, decreased lipase activity is a primary risk factor inobesity. Inhibition of lipase also results in an accumulation of higher fattyacids which contribute to cardiovascular disease. Individuals with cysticfibrosis, Crohns disease, and celiac disease are a particular high risk group fordeficiencies in lipase. Their risk is confounded by exposure to artificiallyfluoridated water. The RoI one of the highest incidences rates for cysticfibrosis, Crohns and celiacs disease in the world.

18. Fluoride inhibits cellular production of lactate. Lactate plays a crucial role in protecting the central nervous systems including neurobiology. The RoI hasone of the highest incidence rates for neurological disorders in the world.

19. Fluoride inhibits arginase. It has been established that arginase inhibitorsincrease the risk of inflammatory diseases and cancers in humans. The RoI

one of the highest incidences rates for inflammatory diseases and cancer in theworld.

20. Fluoride inhibits folate contributing to increased homocysteine levels. Folateis important for the functioning of the central nervous system at all ages ofdevelopment. Folate deficiency induces neurotoxicity due to accumulation ofhomocysteine.

21. Fluoride is an enzyme inhibitor that contributes to hyperhomocysteinemia, orthe accumulation of HCY, in humans. Homocysteine is implicated in many pathological conditions including cardiovascular diseases, neural tube defects,and is now recognised as a risk factor in Alzheimers disease (AD) anddementia. There is also growing evidence that homocysteine plays a role in


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alcoholism, depression and anorexia nervosa. Homocysteine metabolism has been documented as a risk factor of Downs syndrome (DS). Research hasdemonstrated a positive relationship between homocysteine levels andincreased hostile behaviour in schizophrenia. Homocysteine may also be animportant factor in Parkinsons disease. Furthermore, it h as been found that ahigh plasma concentration of homocysteine may contribute to epilepsy. TheRoI has one of the highest incidence rates for neural tube defects, Downssyndrome, cardiovascular disease, depression, schizophrenia, epilepsy andalcoholism in the world.

22. Fluoride has been found to adversely affect collagen and contribute toinflammatory skin diseases such as atopic eczema and psoriasis. The RoI hasone of the highest prevalences of skin diseases internationally significantlyabove European prevalence rates. Skin conditions are the fourth most commonreason for GP visits in Ireland and the prevalence of skin diseases such as skincancer, leg ulcers and atopic eczema has increased steadily in recent decades.Today, between 25% and 33% of the Irish population suffer from adermatological condition at any one time.Elevated prevalences of skindiseases significantly above the global average are also prominent in othercountries with artificial fluoridation

23. Fluoride exposure increases the risk of epilepsy through reducing melatoninand increased homocysteine levels. Epilepsy is the second most commonlyseen neurological condition in primary care worldwide; the adult prevalencerates of epilepsy in the RoI are almost twice the European prevalence rates andare also significantly higher than the prevalence rates reported for NorthernIreland, Scotland, England and Wales.

24. Fluoride as an inflammatory agent contributes to inflammatory bowel disease(IBD). The incidence rates for IBD in the RoI are twice that of non-fluoridated Northern Ireland and the highest incidences of this disease internationally areto be found in countries with artificial fluoridation programmes.

These are not insignificant findings in any sense of the word. Any one should in anormal society demand an immediate end to artificial fluoridation in the interest of public safety.

The scientific evidence is overwhelming, artificial fluoridation is contributing tochronic illness and is directly impacting on the physical, emotional and psychologicalwellbeing of consumers. A simply measure can be taken almost immediately to protect public health that will reduce the burden of chronic disease, that is endingartificial fluoridation of public water supplies. In this context, it is important to notethe Public health approaches in most developed countries worldwide, particularly inEurope has been to either avoid or move away from artificial fluoridation of publicwater supplies on grounds of insufficient evidence to demonstrate its safety and thelong term public health consequences. The evidence in this report not only supportstheir understanding but demonstrates the long term impact of such a policy incontributing to chronic diseases and ill health.


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For your records I also include in attachments, my latest study on the contribution offluoride to chronic inflammatory respiratory diseases in children and adults whichalso includes information on Israel. These findings were presented in October 2013 atan international fluoride conference in the Middle East attended by some of theworlds leading experts in fluoride toxicity to which I was invited to participate as a

keynote speaker. This study documents how fluoride exposure has significantlycontributed to inflammatory respiratory diseases and examines the evidence fromover 30 countries internationally. My research paper was submitted to a leadingscientific journal for peer review and publication in December 2013.

Sincerely yours,

Declan Waugh BSc. CEnv. MCIWEM. MIEMA. MCIWMEnvironmental Scientist and Risk Management ConsultantEnviroManagement Services11 RiverviewBandon,Co. CorkIreland.


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The Contribution of ArtificialFluoridation to the Burden of

Chronic Disease

Report for

The Government of IrelandThe European Commission andWorld Health Organisation

Prepared ByDeclan Waugh BSc. CEnv. MCIWEM. MIEMA. MCIWM

EnviroManagement Services, Bandon, Co. Cork, Republic of Ireland.

January 2014


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Contents

1. Abstract ......................................................................................................................... 1

2. Fluoride and Infant Exposure ........................................................................................ 2 3. Fluoride Exposure of Adults ......................................................................................... 4 4. Fluoride, Endocrine Disorders, Health effects and Pathophysiological Mechanism .... 6

Fluoride exposure increases Calcitonin levels in Humans ............................. 8 5. Fluoride, Impaired Glucose Tolerance, Diabetes and Obesity. ..................................... 9 6. Fluoride Inhibition of Enolase, Health effects and Pathophysiological Mechanisms . 14 7. Fluoride inhibition of Lactate, Health effects and Pathophysiological Mechanisms .. 15 8. Fluoride, Folate, Health effects and Pathophysiological Mechanisms ........................ 15 9. Fluoride inhibition of Lipase, Health effects and Pathophysiological Mechanisms ... 16 10. Fluoride inhibits Calcium Homeostasis ....................................................................... 17 11. Fluoride inhibits Magnesium Homeostasis ................................................................. 18 12. Fluoride inhibition of Manganese metallenzyme arginase .......................................... 19

13. Fluoride inhibition of Cholinesterase and Pulmonary disease .................................... 20 14. Fluoride, Increased production of Free radicals, Oxidative stress and Cancer............ 22 Figure 1. Comparison of Cancer incidence for RoI and European Region ... 28 Figure 2. Global incidence of Cancer ............................................................ 28

15. Fluoride, Increased production of Free Radicals, Oxidative Stress and Neurodegenerative Disorders ...................................................................................... 29

16. Fluoride, Inhibition of Homocysteine, Health effects and PathophysiologicalMechanisms ................................................................................................................. 31

Folate deficiency increases Homocysteine levels......................................... 31 Fluoride inhibition of S-adenosylhomocysteine hydrolase .......................... 32 Health effects of Hyperhomocysteinemia ..................................................... 32

17. Fluoride, Free Radicals and Vascular Disease. ........................................................... 33 18. Fluoride, Inflammation and Disease ............................................................................ 36

Musculoskeletal Pain ...................................................................................... 36 Inflammatory Bowel Diseases ........................................................................ 37 Skin Disorders ................................................................................................ 39

19. Fluoride and Epilepsy .................................................................................................. 42 20. Conclusion ................................................................................................................... 43 References ............................................................................................................................... 44


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The Contribution of Artificial Fluoridation to the Burden of Chronic Disease. Waugh D. 2014

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1. Abstract

It is evident that pro inflammatory inducers such as highly soluble inorganic fluoride,from artificial fluoridation of water, are recent and manmade. The recent increase inchronic inflammatory diseases coincides with the period of commencement offluoridation worldwide. The fact, that most chronic diseases have also risen to prominence during this time (albeit along with an aging population) and importantly,that the highest burdens of inflammatory and other associated diseases are typically to be found in artificially fluoridated countries such as the USA, Australia, Republic ofIreland, New Zealand and Canada would clearly suggest a causal role for artificialfluoridation in contributing to chronic disease burdens. Where exposure to pro-inflammatory agents persists, the response over time may become chronic. This isevident in the accumulation of fluoride in humans living in fluoridated regions whichhave been found to be significantly higher than those of non-fluoridated communities.Because fluoride is a bioaccumulative toxin continued exposure results in significantaccumulation of this toxin in human tissues over the individuals lifetime. In addition,the impact of chronic overexposure of infants to fluoride is resulting in unprecedentedepidemics of metabolic and neurological disorders with catastrophic healthcare,societal and economic consequences. The economic costs alone are staggering and theimplications for future generations are enormous.

This report examines the scientific facts demonstrating chronic overexposure offluoride in infants as well as adults, and the biological mechanisms of how fluoride iscontributing to disease. This report provides the relevant current published scientific

information from peer reviewed scientific journals, from which it is evident that the preponderance of scientific data clearly demonstrates that increasing fluorideexposure of the population through artificial fluoridation is contributing to a widerange of chronic diseases that are prevalent in certain countries today. It is clearlyevident that increased fluoride exposure has a direct inhibitory effect on energymetabolism in human cells and that the inhibitory effect of fluoride on enolase, folate,lactic acid, lipase, arginase, cholinesterase, calcium and magnesium homeostasis, inaddition to inhibition of homocysteine metabolism, combined with fluoridescontribution to increased production of free radicals and oxidative stress, as well asfluoride exposure contributing to elevated calcitonin is having far reachingconsequences for human health, ultimately contributing to a wide range of chronic

diseases that are known to have particularly high prevalences in countries withartificial fluoridation programmes. The evidence is now irrefutable, artificialfluoridation is contributing to low level chronic poisoning of the population and posesa real and immediate threat to life, public health and safety. Immediate action must betaken by public health authorities to end this policy. Additional factors associatedwith artificial fluoridation, including how the chemical intoxication of individualswithout their informed consent is a violation of medical ethics; the noncompliancewith legislation on the use of chemicals that require detailed toxicological andepidemiological evidence demonstrating their safety for human or the environment,and the life cycle of artificial fluoridation which results in the contamination of theentire food chain with highly soluble inorganic fluorides are not addressed in thisreport.


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2. Fluoride and Infant ExposureIt is generally accepted that infants under 12 months are the highest risk group fordeveloping dental fluorosis due to consumption of formula milk feed reconstitutedwith fluoridated water in the first year of life. Dental fluorosis is the most obviousvisible toxic effect of fluoride. It is further known that the condition overwhelminglyapplies to infants who are fed formula milk prepared with fluoridated water. Thisview is supported by UK Medical Research Council (2002) when they reported thatindividuals most likely to have supra-optimal fluoride intakes are formula-fed infantsin fluoridated areas [1].

It is important to acknowledge that for infants up to 6 months of age there are noestablishedSafe Dietary Upper Tolerable Intake Levels for Fluoride exposure. Nevertheless, the U.S Institute of Medicine have reported that the adequate intake offluoride for infants aged 0-6 months of age is 0.01mg/kg/day [2].

Recent risk assessments conducted internationally have concluded that babies fedformula milk prepared with fluoridated water will exceed the established uppertolerable safe level for fluoride exposure for healthy adults [3,4,5].

According to the European Food Safety Authority (2006), the fluoride intake for babies fed formula milk constituted with fluoridated tap water (0.8mg/l) would beapproximately 0.16mg fluoride/kg body weight/day compared to 0.0003-0.0016mg/kg/day for breast fed babies [5]. This represents an alarming 100-533 foldincreased exposure to fluoride compared to breast fed infants. When compared to theadequate intake level reported by the U.S Institute of Medicine it represents a 16 foldexceedance (1600%). Importantly, the EFSA also reported that additional dietary

sources of fluoride, in particular, fluoride exposure from prescribed medications canalso be a major contributor to infant dietary fluoride intake. While the EFSA notedthat this may contribute in some circumstances up to 75% of the total dietaryexposure for infants. This presents yet another public health risk especially influoridated communities as no product information is available to consumers ormedical physicians providing the fluoride contend of medications. Logically, forinfants already overexposed to fluoride from fluoridated formula milk, their exposurefurther increases when other sources of fluoride such as medications are included. Itshould also be noted that the EFSA reported that severe clinical gastrointestinalsymptoms were observed in children administered a single dose of 1mg/kg bodyweight [5]. While these observations did not include infants, Bubenik (2002) reportedthat low melatonin may be associated with ulcerative colitis, gastric ulcers, irritable bowel syndrome, and childhood colic [6]. This latter finding has an obviousimportance considering the high prevalence of infantile colic during the first fewmonths of life in certain countries and especially when one considers that the U.S NRC reported how fluoride can reduce melatonin in humans [7]. Given the obvioussensitivity of new born infants to toxins, such a prolonged chronically high exposureto highly soluble inorganic fluorides, from the consuming fluoridated formula milk,can clearly be expected to compromise their digestive, immune and endocrinesystems.

Interestingly, the Canadian Paediatric Society recommend that no fluoride should begiven before teeth have erupted and no fluoride supplement should be given to an


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infant before six months of age [8]. Furthermore, they recommend that fluorideconcentrations should be stated on any foods or drinks containing fluoride [8].

For older children up to eight years of age the EFSA proposed a Tolerable UpperIntake Level of 0.1 mg/kg [5]. For children older than eight years and adults theEFSA recommended a UL of 0.12 mg fluoride/kg body weight [5].

It is clearlyevident that these UL are significantly exceeded for infants where fluoridated water is

used to prepare formula milk. From a public health point of view these facts arecrucially important. It is in this context, the World Health Authority drinking waterguidelines specify that the Tolerable Daily Intake (TDI) from all sources includingdrinking water should not be exceeded [9].

The WHO recommend that"if the potential exposure from drinking water in anincident is greater than the Tolerable Daily Intake or exposure is likely to be extendedbeyond a few days, then this would require consideration in conjunction with healthauthorities. In such circumstances, it may be possible to target action to avoidexposure at the specific group concerned, such as supplying bottled water for bottle

fed infants." Alternatively, the WHO recommendedthat "such steps can be used on ahousehold basis to reduce exposure and allow the continued use of the supply withoutinterruption." [9]Furthermore, the WHO observed that specific subpopulations, in particular bottle fed infants, are at greater risk from a substance than the rest of the population due to high exposure. The WHO also noted that some geneticsubpopulations may show greater sensitivity to particular toxicity. Based on our previous discussion this would include, for example, individuals with cystic fibrosis,Crohns disease or celiac disease [9].

More recently the European Food Safety Authority commissioned a study identifyinghealth outcomes upon which Dietary Reference Values for fluoride could beestablished [10]. This review only reported on fluoride intake levels below thetolerable upper intake (1.5 mg/day for children aged 1-3 years, 7 mg/day foradolescents and adults 15 years), and only included forms of fluoride that arenaturally present in foods, or approved by the EC for use in foods (potassium fluoride;sodium fluoride) or food supplements (calcium fluoride; potassium fluoride; sodiumfluoride; sodium monofluorophosphate). The review did not include fluoride intakefrom artificially fluoridated water using hexafluorosilicic acid. The review concludedthat few studies existed which met the scientific standards for inclusion criteria andthe majority were assessed as being at high risk of bias. Of critical importance

however the report highlighted that there was a lack of high quality evidence uponwhich DRVs may potentially be based for fluoride; consequently the authors wereunable to provide recommendations for establishing safe dietary intake referencevalues for fluoride. This in itself is an astonishing finding and one which clearlysupports the observations of the US NRC scientific committee when theyrecommended in excess of sixty epidemiology, toxicology, clinical medicine andenvironmental exposure assessments that need to be undertaken in order to fillknowledge gaps in the toxicological assessment and long term health effects offluoride ingestion. Based on these findings it is apparent that Public HealthAuthorities in fluoridated countries are negligent in protecting the most vulnerable insociety at their most sensitive period of development, from chronic overexposure to

fluoride.


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3. Fluoride Exposure of AdultsThe total dietary exposure of an individual is the sum of exposure from all food andother sources consumed in a day. Because of the wide variability of exposures tofluoride it is impossible to control the total dietary intake of fluoride for anyindividual. Nevertheless the risk factors for increased exposures to fluoride increasesignificantly when public water supplies are fluoridated and dietary exposures cannot be controlled to protect the health and welfare of citizens when such a policy isenacted. This view is supported the European Food Safety Authority (2006) whoreported that while the intake of fluoride from water can be estimated with somecertainty an estimation of fluoride intake from other sources is prone to the influenceof a wide variety in individual habits[5]. Alarmingly, the EFSA reported up to 50 foldvariations in fluoride content of human bone depending on fluoride intake.

Importantly, the NRC reported that the dietary intake of fluoride by adults in the UKis expected to be high, due largely to the consumption of popular beverages such as

tea [11]. The NRC committee specifically noted that the fluoride content ofcommercial instant teas can be substantial and that consumption of tea can result inindividual dietary exposure of up to 9mg of fluoride a day [11]. Importantly, the U.S National Academy of Science (NAS) recommends a Dietary Reference Intakes (DRI)of 4mg per day for healthy adults [12].

Ireland has the highest consumption of tea in the world surpassing the UK in theconsumption of tea, consuming on average 20% more tea than the average UK teadrinker. Consequentially the potential fluoride dietary intake for a significantsubgroup of the adult population in Ireland is greater for many individuals comparedto the risk for consumers in the UK. A further and significant risk factor for the

population of Ireland is that less than 10% of the UK population compared to (75-80%) of the Irish population are provided with artificially fluoridated water. Boilingfluoridated tap water increases the concentrations of fluoride in water and food.Where public water is used for preparation of food products significant increases influoride content have been noted [5.13,14].

A current study by Chan et al., (2013) examined the dietary fluoride exposure of theUK population from tea consumption. The study determined the fluorideconcentrations in a selection of 38 commercial teas sold in the UK market, includingthe leading commercial supermarket brands which are also sold in the Irish market.The study determined that many of the teas contained elevated concentrations offluoride up to 8.85 mg/L [15]. These measurements were made on tea infusions prepared with deionised water. Importantly, their findings on fluoride concentrationsin tea are in agreement with published data reported by researchers globally [5,16-51]. While the authors concluded that detrimental health effects could occur when an adultconsumes 1 L of tea daily, especially when prepared using a UK supermarketeconomy brands, it should be noted that the concentration of fluoride in tea beveragesis further increased by using boiled fluoridated water to prepare the product. Theincreased exposure was acknowledged by the European Food Safety Authority whoreported that if fluoridated water were drunk and used for the preparation of food andtea (1-2 L of water/day; 500 mL of tea (2 cups) with a fluoride concentration of 5mg/L) 3.5 to 4.0 mg fluoride would be added to the daily dietary intake of anindividual compared to consumers living in non-fluoridated areas [5]. The EFSAreported that even more extreme scenarios are possible and not completely unrealistic.


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This is reflected in the ROI where many adults consume 6-8 cups of tea daily madeusing boiled fluoridated water. Based on the measured concentrations of fluoride intea, the total daily dietary fluoride intake for many individuals will be multiples of therecommended DRI as recommend by the NAS and will significantly exceed thetolerable upper intake level of 7mg fluoride per day as recommended by the EFSA.

More importantly, fluoride exposures will vastly exceed the levels that have beenreported to alter thyroid function in both healthy and iodine deficiency populations.These findings are of interest not just for endocrine disorders, which is discussedlater, but also cancer risk. Shafique et al., (2012) in a large cohort prospective study ofScottish males reported that tea may be a potentially modifiable and highly prevalentrisk factor for prostate cancer in men [52]. The association of fluoride exposure andincreased calcitonin is well established [11]. Calcitonin is an amino acid polypeptidehormone secreted by the parafollicular cells of the thyroid gland. Increased calcitoninis known to play a pivotal role in the pathogenesis of prostate cancer [53, 54,55].

Vandenberg et al. (2012) reported that water fluoridation chemicals were as endocrinedisrupting chemicals (EDCs) at low dose levels [56].According to the EuropeanEnvironment Agency (2012) there is evidence linking foetal exposure to EDCs with prostate cancer [57].

Furthermore, Woodward and Pedoe (1999) in a nationwide large scale random population study of men and women aged 40-59 years found increased coronary riskfactors, coronary risk and mortality for tea drinkers compared to coffee drinkers [58].Critically, these observations support the findings of Gutowska et al., (2010) whoreported that fluoride may be atherogenic, promoting the formation of fatty depositsin arteries [59] and of Kanbay et al. (2012) when they reported that increasedcalcitonin levels are associated with greater severity of coronary artery disease [60].

It is not possible for individuals to estimate their risk of exposure or control theirdietary intake of fluoride when they are not provided with any information on thefluoride levels of foodstuffs or medications purchased. This concern was addressed by the WHO over twenty years ago when they recommended that the fluoride contentshould be printed on products, especially for countries with large artificial wateruoridation programmes due to increased fluoride exposures of their populations [51].

Based on these indisputable scientific facts, it is obvious that artificial fluoridation

cannot in any way be regarded as safe. It is a scientific fact that artificial fluoridationis contributing to chronic fluoride overexposure and detrimental health effects amongthe wider population.

The known health effects will be discussed in the following sections.


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4. Fluoride, Endocrine Disorders, Health effects andPathophysiological Mechanism

Hypothyroidism affects 5 10% of the general population with increased prevalence in olderindividuals and females. Hyperthyroidism is less common, affecting 1% of thegeneral population [61]. It is generally accepted that the thyroid gland is one of themost sensitive organs because of its histopathological and functional responses toexcessive amounts of fluoride [62-65]. Fluoride is known to interfere with thyroidgland function and thereby can adversely affect growth and cause degenerativechanges in the central nervous system and impairment of brain function in humansand animals [66-68]. In a review published over 30 years ago, McLaren discussed theaccumulation of F in the thyroid and its possible relationship to morphological andfunctional changes [69].

It is estimated that 2 billion individuals globally have an insufficient iodine intake

[70]. In Europe it is estimated that 47.8% of school-aged children and 46.1% of thegeneral population are deficient in iodine [71] and it has been reported that up to 50%of pregnant women in the UK and Ireland may be significantly iodine deficient [72].Secondly, in fluoridated countries regardless of iodine status, a large percentage of theadult population are exposed to fluoride at levels that are harmful to their generalhealth. Iodine deficiency produces a thyroid hormone pattern consistent withsubclinical hypothyroidism (ScH) [73]. According to the NRC (2006) ScH can cause bone demineralization, is associated with increased cholesterol concentrations,increased incidence of depression, diminished response to standard psychiatrictreatment, cognitive dysfunction, and, in pregnant women, decreased IQ of theiroffspring [11].

In regards to thyroid function and general health, it is important to recognize thatthyroid hormone concentrations are correlated with adverse effects in organ systemsother than the nervous system in the adult, including the cardiovascular system andcontrol of serum lipids [74,75,76] pulmonary system [77,78,79] and kidney. Totalcholesterol, low density lipoproteins (LDL), nonhigh density lipoproteins (non-HDL),and triglycerides increase linearly with increasing TSH, and HDL decreasesconsistently with increasing TSH across normal reference ranges without evidence ofany threshold effect [80]. Within the reference ranges for TSH, there is a linear positive association between TSH and both systolic and diastolic blood pressure [80].Intimal medial thickness (IMT), a measure of atherosclerosis and predictive ofcoronary vascular disease and stroke, is inversely related to free T4 after controllingfor lipids, clinical factors, and thyroid autoantibodies [81]. Not surprisingly,alterations in thyroid homeostasis have been found to increase the risk ofcardiovascular disease [82-84]. Rodondi et al., (2006) in a meta-analysis of 14epidemiologic studies found an overall increase in risk of coronary heart disease(CHD) of over 65% in those with subclinical hypothyroidism (elevation in TSH withnormal T4) [85].Therefore, epidemiologic as well as mechanistic and therapeuticevidence substantiates the concern that thyroid disrupting chemicals may adverselyaffect cardiovascular risk in humans by reducing serum T4.


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A recent scientific review by Vandenberg et al. (2012) examining low dose exposuresto endocrine-disrupting chemicals (EDCs) lists water fluoridation additives added to prevent dental caries as EDCs with reported low dose effects in animals or humans[56]. The report documents that EDCs inhibit insulin secretion, inhibit parathyroidhormone secretion and reduce thyroid hormone output [56]. Importantly, the U.S National Academies reported that in humans effects on thyroid function wereassociated with fluoride exposures of 0.05-0.13 mg/kg/day when iodine intake wasadequate and 0.01-0.03 mg/kg/day when iodine intake was inadequate [11]. Thisexposure equates to a total dietary fluoride intake of between 0.7 - 3.5mg per day atwhich thyroid function may be impaired. It is an established fact, as noted by theEuropean Food Safety Authority, that the levels of dietary exposure ranging between0.7 and 3.5mg/day are greatly exceeded in fluoridated communities [8].

US National Research Council Review of Fluoride in Drinking Water, 2006Fluorideexposuremg/kg/day

Total FluorideIntake mg/day

Altered thyroid function when iodine intake adequate 0.05-0.1 3.5-9.1Altered thyroid function when iodine intake inadequate 0.01-0.03 0.7-3.5 NAS (National Academy of Science) (2004). Dietary reference intakes (DRI)*The NAS, recommended dietary reference intake (DRI) offluoride a day for adults

4 mg

Chan et al (2013) Human exposure assessment of fluoride from tea*Fluoride concentrations in black tea infusions prepared withdeionised water ranged up to 8.85 mg/LDietary fluoride intake when 5 cups of tea consumed per daymade with deionised water

0.15 Up to 11mg

Dietary fluoride intake when 5 cups of tea consumed per daymade with fluoridated water

0.17 Up to 12mg

European Food Safety Authority, 2006**Total Dietary intake from all sources when not usingfluoridated water, no fluoridated salt, fluoridatedsupplements and no fluoride containing dentifrice

0.5-1.2

Total dietary intake without fluoride from toothpaste takeninto account but including intake from drinking fluoridatedwater and using it for preparation of food and tea (1-2L ofwater/day; 500ml of tea with a fluoride concentration of5mg/l)

>6mg

Using the current data from Chan et al. (2013) the totaldietary intake from drinking fluoridated water and using itfor preparation of food and tea (1-2L of water/day; 5 cups oftea per day with a fluoride concentration of 8.85mg/l) andexcluding fluoride from toothpaste or other sources such asmedications.

>13mg

Note:*NAS (National Academy of Science) (2004). Dietary reference intakes (DRI): Recommended intakesfor individuals. Food and Nutrition Board, Institute of Medicine, National Academies.**Laura Chan , Aradhana Mehra, Sohel Saikat, Paul Lynch. Human exposure assessment of fluoridefrom tea (Camellia sinensis L.): A UK based issue. Food Research International 51 (2013) 564 570

*** European Food Safety Authority, Opinion of the Scientific Panel on Dietetic Products, Nutritionand Allergies on a request from the Commission related to the Tolerable Upper Intake Level ofFluoride, EFSA Journal 2005 192, 1-54


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F lu ori de exposur e in creases Calcitonin levels in H umans

Calcitonin is an amino acid polypeptide hormone secreted by the parafollicular cellsof the thyroid gland. The US National Research Council reported that elevatedCalcitonin has been noted at fluoride intakes as low as 3.8 mg/day in humans(approximately 0.06 mg/kg/day) and was found routinely at intakes of at least 9mg/day (approximately 0.15 mg/kg/day) [11]. The NRC reported that intakes of 9mg per day or higher are expected in countries where there is a high consumption of tea[11]. As noted previously, the European Food Safety Authority, has established thatdietary fluoride intake levels of greater than 6.5mg per day are expected in fluoridatedcommunities [5].

The importance of these findings are self-evident, especially when research hasdemonstrated that increased calcitonin levels are associated with greater severity ofcoronary artery disease [60], inflammatory lung disease, lung cancer, breast cancerand thyroid cancer [86]. In addition, Shah et al. (1994), Sabbisetti et al. (2005) andSha et al. (2008) reported that elevated calcitonin plays a pivotal role in the pathogenesis of prostate cancer [53,54,55] elevated serum levels of calcitonin havealso been identified in many other cancers including thyroid, lung and breast,leukemia, ovarian and pancreatic cancers [86,352-357]. Research has also establishedthat elevated calcitonin is associated with major depressive disorders [87] as well ashaving a causative role in neurological disorders such as migraine [88, 89].

The European Medicines Agencys Committee for Medicinal Products for HumanUse (2012) determined that elevated levels of the hormone calcitonin increases cancerrisk and have advised that calcitonin medications no longer be prescribed by medical physicians [366]. In summary, based on our previous discussion it is clear that:

Individual dietary intake of fluoride can vary significantly depending onconsumption of fluoridated water, tea and other foodstuffs as well as use ofmedications.

The fluoride exposure that may affect thyroid function in healthy individualsis greatly exceeded for many individuals living in fluoridated communities.

The margin of risk for effects on thyroid function is increased up to 5 fold inindividuals with iodine deficiency.

Up to 48% of the European population have been reported to be deficient iniodine.

Consequently, a very significant percentage of the population living influoridated communities will be adversely affected by increased fluoride

exposure from artificial fluoridation of water. In countries where there is a high consumption of tea, dietary fluoride intakesfor consumers will be substantially higher.

The RoI and the UK and the largest consumers of tea per capitainternationally, therefore their populations will have substantially greaterdietary fluoride intake.

The use of fluoridated water in preparing tea beverages can increase thedietary intake of fluoride by up to 13%.

Fluoride exposure arising from consumption of fluoridated water increases the production of calcitonin. Elevated calcitonin has been identified as acontributory risk factor in heart disease, inflammatory lung disease, depressivedisorders, migraine and cancer.


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5. Fluoride, Impaired Glucose Tolerance, Diabetes and Obesity.

Pre-diabetes exists when blood glucose is elevated, but not as high as type 2 diabetes.Hyperglycemia is a condition characterized by high blood sugar levels. When thisoccurs during pregnancy, but not prior to pregnancy, it is called gestational diabetes.Type 1 diabetes is an autoimmune disease that occurs when the pancreas no longer produces any insulin or produces very little insulin. It usually develops in childhoodor adolescence and affects up to 10% of people with diabetes. There is no cure. It istreated with lifelong insulin injections and careful attention to diet and physicalactivity. Type 2 diabetes is a disease that occurs when the pancreas does not produceenough insulinto meet the bodys needs and/or the body is unable to respond properlyto the actions of insulin (insulin resistance). Type 2 diabetes usually occurs later inlife (although it can occur in younger people) and affects approximately 90% of people with diabetes. There is no cure.

In North America and elsewhere, the incidence of diabetes has reached epidemic proportions with further increase continuing [90]. The increases appear to be most profound in countries with artificial fluoridation including Ireland, Australia, NewZealand, Brazil and Mexico. In diabetes, the main cause of microcirculatory damageis the consequence of non-enzymatic glycosylation of proteins, which is theconsequence of high extracellular glucose levels [91].

The effect of fluoride on carbohydrate metabolism was noted as far back as the1930s and 40s when fluoride was identified as a potent inhibitor of enolase [92,93].Vasudevan et al. (2011) reported that fluoride will inhibit the enzyme, enolase, andconsequently the glycolysis [94]. In 1950, Professor Rapp published a report titled

The Pharmacologic Effects of Fluorides in which he reported on fluorides effectsupon enzymes, cells and calcifying tissues [95]. In the case upon enzymes he notedthat there is a selective activity demonstrated in its effects. Since enzymes can beconsidered to be complexes consisting of proteins, vitamins, and a metalliccomponent, and since the metal portion of each enzyme is not identical with that ofanother enzyme, it follow that those enzymes which have metallic componentscapable of being rendered insoluble, or nor-available, will be affected by the presenceof fluorides. According to Rapp one of the most important systems of enzymes thatare susceptible to fluorides are those involved with phosphate transport. The effect of phosphatases and phosphorylases become important from several points of view. Inthe first place, phosphate transporting enzymes are important in the absorption ofcarbohydrates from the small intestine. Rapp noted that when these enzymes areabsent or poisoned in any manner, sugar absorption takes place only slowly.Secondly, these enzymes are also important in the utilization of carbohydrates in the body. Indirectly they are also concerned with the metabolism of fats and proteins. Inthe presence of an adequate amount of fluorides, these enzymes are poisoned andnormal sugar metabolism is disturbed. Rapp compared the blood sugar, muscle andliver glycogen, and blood lactic acid concentrations under the influence of fluoridesand observed that the results indicate that the effects are very similar to those obtainedin diabetes, and suggested that the presence of fluorides seems to interfere withmetabolic systems similar to those affected by an insufficiency of insulin. In regardto the effects of fluoride on cellular function, Rapp further noted that all cells areaffected by fluoride to a greater or lesser degree. The extent of the effect on the cellseems to be directly related to the cells dependence on carbohydrate metabolism [95].


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The U.S National Academies (2006) reported that among the major endocrine effectsof fluoride exposure is impaired glucose tolerance and noted that the primarymechanism appears to involve inhibition of insulin production. This was a matter ofsome concern to the scientific committee given the increasing prevalence of diabetesmellitus; accordingly the scientific committee advised that any rol e of f luori deexposur e in the development of impair ed glucose metaboli sm or diabetes ispotenti all y sign ificant. [11].

Rigalli et al. (1990) reported that fluoride had an inhibitory effect on the secretion ofinsulin [96]. Garcia et al. (2009) demonstrated that fluoride exposure impairs glucosetolerance via decreased insulin expression and oxidative stress [97]. O Barbier et al.(2010) reported that that biologically relevant doses of fluoride can result inimpairment of glucose tolerance or increased blood glucose and decreased insulinsynthesis [98].

Numerous other studies have demonstrated that impaired glycemic control and insulinrestance are risk factors for depressive disorders such as major depression [99-102]

Balasubramanyam et al. (2010) reported that fluoride is a risk factor in both thedevelopment of obesity and diabetes [103].

A recent scientific review by Vandenberg et al. (2012) examining low dose exposuresto endocrine-disrupting chemicals (EDCs) lists water fluoridation additives added to prevent dental caries as EDCs with reported low dose effects in animals or humans[56]. The report documents that EDCs inhibit insulin secretion, parathyroid hormonesecretion and reduce thyroid hormone output. A current publication on endocrinedisrupting chemicals by the Inter-Organisation Programme for the SoundManagement of Chemicals (IOMC) for the WHO and United Nations EnvironmentProgramme also lists water fluoridation chemicals as low dose EDCs [104]. Thereport highlights how obesity, diabetes and metabolic disorders are due to disruptionof the energy storage energy balance endocrine system and thus are potentiallysensitive to EDCs. According to the IOMC fat development and weight gain is a goodexample of complex physiological systems that are influenced by endocrinedisruptors. There are a number of endocrine disruptors that have been shown to affectweight gain, insulin sensitivity and glucose tolerance indicating a potentiallyimportant role for endocrine disruptors in the development of obesity type 2 diabetes

and metabolic syndrome [104]. The elements of the endocrine system that controlweight gain and metabolism/energy expenditure include the adipose tissue, pancreas,GI tract, liver, skeletal muscle, bone and brain, and endocrine disruptors couldspecifically and directly affect each of these tissues by interfering with their varioushormone systems [104]. The NRC review (2006) identified how fluoride and fluoridecompounds may interfere with each of these tissues [11].

Ropero et al., (2008) and Sargis et al., (2010) noted that because obesity is anendocrine-related disease/dysfunction, it is potentially sensitive to endocrinedisrupting chemicals [105, 106]. According to the IOMC current research suggests that exposure to some endocrine

disrupting chemicals during pregnancy can lead to altered cholesterol metabolism,weight gain and type 2 diabetes in the offspring later in life [104]. This view is


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supported by Ong et al., (2000) and McAllister et al., (2009) when they reported thatthere is evidence that the obesity risk may begin early in life, during pregnancy, andin early childhood and that rapid weight gain, in the first few months of life, isassociated with obesity later in life [107,108].

The U.S National Academies (2006) reported that fluoride is a pro-inflammatoryagent that increases the inflammatory response to irritants in humans; consequentlyexposure to fluoride increases the proinflammatory status [11]. In 2012, in a review paper on glycolysis in the control of blood glucose homeostasis, the ChineseAcademy of Medical Sciences reported how increasing proinflammatory status produce pro-hyperglycemic factors and bring about hyperglycemia and insulinresistance [109].

Peterson (1954) reported the relationship between maternal glucose metabolism,gestational diabetes (hyperglycemia) and birth weight has been attributed to increasednutrient transfer to the fetus due to diminished insulin sensitivity leading to maternalutilization of free fatty acids for energy [110]. The fetus is thought to respond byincreasing insulin secretion, with increased fat storage to prevent fetal hyperglycemiaand ultimately increased fetal weight [110]. Hodge and Smith (1965) reported thatfluoride inhibits lipase resulting in an accumulation of fatty acids [111]; fatty acidsand obesity induce endoplasmic reticulum (ER) stress in liver, which suppressesinsulin production and contributes to diabetes [112]. Scholl et al. (2001) also reportedthat birth weight increased with increasing maternal glucose [113]. In addition, it wasreported that maternal complications increased twofold or more with high glucoseconcentrations and included cesarean section and clinical chorioamnionitis [113].According to the authors, their findings suggest that higher, but seemingly normalmaternal glucose concentration predisposes to or is a marker for placentalinflammation and infection [113]. Hiller et al. (2007) also reported that increasinghyperglycemia in pregnancy (gestational diabetes) is associated with an increased riskof childhood obesity [114].

In childhood, insulin resistance associated with hyperinsulinemia is a major riskfactor for the development of decreased glucose tolerance in obese children.Chamberlain and Burroughs (1962) reported that low levels of fluoride result in partial blocking of normal carbohydrate metabolism and that lower magnesium levelsin the presence of fluoride significantly reduced metabolic pathways of cellulosedigestion. This inhibition was further increased when low levels of manganese are

combined with low levels of magnesium [115]. The evidence of fluoride ability tocontribute to diabetes was also reported by Tokar et al (1992) who documented thatdecreasing insulin concentration and increasing of the C-peptide levels in blood serumwere caused by the fluorine intoxication [116].

Available evidence therefore clearly suggests that the risk of obesity in children andadults increases with increasing exposure to fluoride. Epidemiological data supportsthis observation. According to a recent OECD report the top five OECD countrieswith the highest incidence of adult obesity are the United States, Mexico, NewZealand, Chile and Australia [117]. It is an acknowledged fact that artificialfluoridation is practiced in each of these countries. The prevalence of obesity in the

U.S is 35% for males and 36% for females, Canada 37% for males and 23% for


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females, Australia 35.6% for males and 21% for females, New Zealand 25% formales and 26% for females [118].

In Ireland, based on the findings from the 2008-10 National Adult Nutrition Survey(NANS), estimated prevalence of overweight in adults is 37%, with a further 24%meeting current body mass index (BMI) criteria for obesity with 26% for males and21% for females documented as obese[119]. Alarmingly the report noted that the prevalence of obesity in 18-64 year old adults has increased significantly between1990 and 2011, from 8% to 26% in men, and from 13% to 21% in women. Thiswould place the RoI in sixth place among the top OECD countries with adult obesity,all of which practice artificial fluoridation. The rates of adult obesity in these sixcountries are more than twice that of countries in the European region, where obesityrates among adults ranged from 6-13% [117].

Given the documented overexposure of infants to fluoride from consumption offormula milk constituted with artificially fluoridated water research would suggestthat the risk of obesity is greater for infants. It is noteworthy therefore that Whelton etal (2007) reported the prevalence of obesity in boys and girls in RoI at 7 and 8%respectively [120]. This compares to 2.6 and 2.7% for the Netherlands, 2.8 and 2.8%for Norway, 3.7 and 1.4% for Sweden 3.6 and 3.7% for Poland, 6 and 5.6 % for Italy,5.8 and 4.2% for Iceland [121]. Furthermore, L.A. Moreno et al. (2011) reported thatIreland had the highest prevalence rates of overweight and obese infants (27.7%).among preschool children 0-6 yrs of age within the European region [121].

It is acknowledged fact that within the European region Ireland is the only countrywith a policy of mandatory fluoridation of public water supplies, consequently itschildren are the most overexposed to fluoride within the European region.

It should also be noted that glucose intolerance is often a gateway to developing type2 diabetes [122]. Type 1 diabetes is associated with autoimmune thyroid disease(AIT), celiac disease (CD), Addisons disease (AD), and other autoimmune diseases.Thyroid disorders remain the most frequent autoimmune disorders associated withtype 1 diabetes [123]. Barker (2006) reported that the prevalence of autoimmunethyroid disease in the population with type 1 diabetes has the potential to affectgrowth, weight gain, diabetes control, menstrual regularity, and overall well-being[123].

The Russian Academy of Sciences recently published a review (2012) of scientificliterature on the molecular toxicity of fluoride, and noted how fluoride inducesendoplasmic reticulum (ER) stress [124]. The endoplasmic reticulum (ER) is acellular compartment responsible for multiple important cellular functions includingthe biosynthesis and folding of newly synthesized proteins destined for secretion,such as insulin. Xu C et al. (2005) reported that accumulating evidence suggests thatER stress plays a role in the pathogenesis of diabetes, contributing to pancreatic -cellloss and insulin resistance [125]. ER stress has also importantly been linked obesityand insulin resistance in type 2 diabetes. Disturbances in the normal functions of theER lead to cell death if ER dysfunction is severe or prolonged. Important roles forER-initiated cell death pathways have been recognized for several other diseases,

including diabetes, heart disease, hypoxia, ischemia/reperfusion injury and neuro-degeneration [125].


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Researchers Menoyo et al. (2005) and Lin et al. (1976) demonstrated the effect offluoride on glucose metabolism using in vivo and in vitro experimental models andconfirmed that biologically relevant doses of fluoride result in impairment of an oralglucose tolerance test and decreased insulin synthesis [126,127]. It has also beenreported by Montalvo et al. (2009) that fluoride exposure regulates insulin geneexpression in murine beta pancreatic cells, resulting in reduced insulin secretion[128]. Oberley (1988) reported that oxygen radicals are not only involved in the causeof diabetes; they also appear to play a role in some of the complications seen in long-term treatment of diabetes [129]. Importantly, Trivedi et al. (1993) demonstrated thatimpaired glucose tolerance was reversed when excess fluoride from the water waseliminated [130].

It seems reasonable to suggest that increasing fluoride exposure, as a result offluoridation, has resulted in increasing pro-inflammatory status contributing toincreasing maternal glucose concentrations, increasing fetal growth and pregnancycomplications including cesarean section, while also contributing to increasedchildhood obesity and the prevalence of depressive disorders. Taken together, thesefindings are very significant especially considering the dramatic increase indepressive disorders and childhood obesity in fluoridated countries combined with thealarming increase in cesarean section.

The role of fluoride in impaired glycemic control and insulin resistance as well as promoting free radical production and oxidative stress clearly must be regarded assignificant especially given the total dietary exposure of the Irish population tofluorides from consuming artificially fluoridated water and fluoride contaminatedfood products combined with their consumption of tea, which is very high in fluoride.This is particularly alarming given the recent published findings on dietary fluorideexposure of the UK population which concluded that a significant percentage werechronically exposed to fluoride at levels that were detrimental to their health andgeneral wellbeing [12]. This conclusion was made based on the measured fluoridelevels in over thirty individual tea products all prepared with non fluoridateddeionised water. Ireland has the highest consumption of tea per capita in the World,above that of the UK and beverages are prepared in Ireland using fluoridated water,consequently the risk of chronic overexposure to fluoride is much greater forconsumers in the RoI.

Based on the scientific evidence previously discussed, it is obvious that the exposure

of the Irish population to fluorides must be examined in the context of the increased prevalence of diabetes and obesity within the population. Evidence suggests that the populations exposure to fluorides is directly contributing to these chronic diseases.According to the HSE, it is thought that one in 20 people in Ireland have diabetes withhalf still undiagnosed and Type II diabetes is increasing rapidly due to increasinglevels of obesity [131]. According to Diabetes Ireland the prevalence of diabetes inIreland is 6.1 per cent of the population compared to 3.8% for Northern Ireland and4.45 % for the UK [132]. Diabetes Ireland reports that there are 200,000 people withdiabetes and a further 200,000 who have diabetes but are unaware that they have thecondition, in addition they report that a further 250,000 people have impaired glucosetolerance or "pre-diabetes" of which 50% will develop diabetes in the next 5 years if

lifestyle changes are not made [133]. Type I (insulin dependent) diabetes is increasingin children, particularly in under-fives while Type 2 (non-insulin dependent) diabetes


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is increasing across all age groups. In the RoI, the incidence of type 1 diabetes is 16.8 per 100,000, which is above the European average [342]. The largest studyundertaken in the RoI to date involving 8,800 people without a prior diagnosis ofdiabetes, aged 45 to 75 years, chosen randomly to attend for clinical evaluation and afasting plasma glucose test, reported an alarming 11% have tested positive forDiabetes and Pre Diabetes [135]. These findings suggest that diabetes prevalence ismuch higher than previously reported and considering that the Department of Healthhas reported that people with diabetes are five times more likely to require hospitaladmission and the risk of major medical complications for people with diabetes is upto 11 times that for people without diabetes [131] present a dire forecast for publichealth in Ireland.

6. Fluoride Inhibition of Enolase, Health effects andPathophysiological Mechanisms

The interference of fluoride in normal carbohydrate metabolism is well established.Warburg and Christain (1941) determined that fluoride inhibits enolase by producinga magnesium fluorophosphate which displaces magnesium from the enzyme surfaceand forms an inactive complex with the enolase [136]. Utter and Werkman (1942)found that the magnesium ion needed with enolase for converting 2-phosphoglycericacid to phosphopyruvic acid was precipitated by fluoride as an insolublefluoromagnesium-phosphor-protein complex [137]. Chamberlain and Burroughs(1962) reported that low levels of fluoride result in partial blocking of normalcarbohydrate metabolism and that lower magnesium levels in the presence of fluoridesignificantly reduce metabolic pathways of cellulose digestion [115]. This inhibition

was further increased when low levels of manganese are combined with low levels ofmagnesium [115].

Enolase is the enzyme responsible for the reversible conversion of D-2- phosphoglycerate (2PGA) and phosphoenolpyruvate (PEP) in glycolysis andgluconeogenesis, two metabolic pathways that are often vital for cellular function[138]. In addition to its innate glycolytic function new evidence has been recently presented to suggest that enolase plays an important role in several biological and pathophysiological processes including autoimmune disorders, cardiovascular health,inflammatory respiratory disease, cancer, Alzheimer's disease, rheumatoid arthritis,inflammatory bowel disease and general disease prevention[138,139,140]. Wygrecka

et al. (2009) furtherreported that -enolase plays a central role in regulating cellularinflammatory response and in inflammatory lung disease [140]. Thus, inhibition ofenolase by fluoride in addition to fluoride exposure increasing calcitonin levels provides another potential link between exposure to fluoride and inflammatorydisease.

The interference of fluoride in fat metabolism has also been documented. Johnson andLardy (1950) found evidence to suggest that fluoride inhibits fatty acid oxidation atsome step prior to the formation of B-keto acids and subsequent to the oxidation ofthe unsaturated fatty acid [141]. Geyer et al. (1950, 1951) in investigating fatmetabolism found that the utilization of octanoic acid was reduced by fluoride[142,143]. Hodge and Smith (1965) reported that fluoride inhibits lipase resulting inan accumulation of fatty acids [111].


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7. Fluoride inhibition of Lactate, Health effects andPathophysiological Mechanisms

Glycolysis may be defined as the enzymatic conversion of carbohydrate into lactate.Recent evidence, and new lines of investigation, now place lactate as an activemetabolite, capable of moving between cells, tissues and organs, where it may beoxidised as a fuel or reconverted to form pyruvate or glucose [144]. There is alsomounting evidence in support of lactate utilisation in the brain [145], via theastrocyte neurone lactate shuttle, a system clearly capable of affecting substratedelivery and neurone function [146,147]. Sanchea-Abarca et al. (2001) reported thatlactate is an important metabolic substrate for the brain during the postnatal periodand also plays a crucial role in the traffic of metabolites between astrocytes andneurons [148]. Imagawa et al. (2006) reported that lactate plays an important role inthe central nervous system as a metabolic substrate between neurons and astrocytes[149].

Philp et al. (2005) reported that lactate may act as a metabolic signal to specifictissues, becoming a metabolite pseudo-hormone as well as having a role in whole- body coordination of sympathetic/parasympathetic nerve system control in addition to playing a role in maintaining muscle excitability during intense muscle contraction[144].

It is long known that fluoride inhibits cellular production of lactate [150-153]. Astleset al (1994) reported that fluoride also rapidly inhibited production of lactate in whole blood [154]. In a study on energy metabolism in human erythrocytes Feiget al (1971)reported that lactate production was immediately and drastically curtailed in the

presence of fluoride while the rate of glucose utilization was reduced more gradually[155]. The authors concluded that fluoride exerts multiple effects on erythrocyte physiology and metabolism. Fluoride inhibited membrane ATPase 40% at 1mole/litre and completely at 5 and 10 moles/litre [155]. This finding is particularrelevance to fluoridation of drinking water as Guyet al (1976) reported that theconcentration of fluoride in blood plasma for residents living in fluoridatedcommunities was 1 mol/litre [156].

8. Fluoride, Folate, Health effects and PathophysiologicalMechanisms

The folic acid cycle is an important metabolic pathway that provides intermediates forthe reactions of nucleotide synthesis and cellular methylation [157]. Folate isimportant for the functioning of the central nervous system at all ages ofdevelopment. Its metabolism provides a methyl, group, via its metabolite 5-methyltetrahydrofolate, which is necessary for the remethylation of the neurotoxicamino acid homocysteine back to methionine, an essential amino acid that plays a keyrole in the generation of methyl groups required for numerous biochemical reactions.Deficiencies in folate induces homocysteine accumulation [158]. Folate deficiencyinduces neurotoxicity by multiple routes, including increasing cytosolic calcium and

oxidative stress via increasing levels of the neurotoxin homocysteine (HC), andinducing mitochondrial and DNA damage[159].


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It has been suggested that polymorphisms in genes that encode folate-metabolizingenzymes may act as potential risk factors for Down syndrome (DS), through thealteration of maternal folic acid metabolism, leading to centromeric hypomethylationand chromosomal nondisjunction [160]. Wald et al. (2002 reported that elevated plasma homocysteine concentrations are associated with folate deficiency and have been associated with increased risk of ischaemic heart disease and stroke in adultlife[161]. An elevated risk of DS has also been observed in the presence of elevatedHHcy concentration [162,163]. Poor folate status has been associated with increasedrisk of cancer, especially colon cancer, possibly due to abnormal synthesis andmethylation of DNA[164]. Furthermore, folate deficiency has been linked toabnormal mental function[165].

The metabolism of Folate is a glucose dependent process which is susceptible tometabolic poisons such as fluorides [166-169]. Furthermore while it is known thatfolate deficiency induce neurotoxicity by multiple routes, it is less well known thatfolate deficiencies can also compromise health by altering calcium homeostasis [170].Fluoride is known to induce or exacerbate calcium deficiency by decreasing calciumabsorption in the gastro-intestinal tract, thus increasing the bodys calciumrequirements [11]. Logically, therefore the health risks for individuals with low folateintake, and low calcium intake are compounded with increasing fluoride exposure.For example, multiple studies have demonstrated that the risk of developingcolorectal cancer is increased when both folate and calcium intake are low [171-174].It is noteworthy also that Fenech et al. (2005) reported that high calcium intake protects against the genome damaging effects of folate deficiency while low calciumintake exacerbate the effects [175]. Considering that folic acid deficiency is one of themost common vitamin deficiency worldwide [176], it is reasonable to suggest that any possible association between fluoride exposure, fluorides inhibition of glucosemetabolism, fluorides role in altering calcium homeostasis and fluorides role ininhibition of S-adenosylhomocysteine hydrolase in combination with lower folatelevels increasing homocysteine concentrations while also contributing to calciumdeficiencies is significant.

9. Fluoride inhibition of Lipase, Health effects andPathophysiological Mechanisms

Lipase is an enzyme that the body uses to break down fats like cholesterol andtriglycerides from ingested foods so they can be absorbed in the intestines. Lipase is primarily produced in the pancreas but is also in the mouth and stomach. Low lipaselevels are to be found in Individuals with cystic fibrosis, Crohn's disease, and celiacdisease. Among individuals with conditions that can contribute to a lipase deficiency,there is the potential for problems to develop, such as prostate disorders, highcholesterol, an increased risk for diabetes, and difficulty losing weight [177,178].Langin et al. (2005) reported that decreased lipase activity is a primary risk factor inobesity [179].

Fluoride has been demonstrated to inhibit liver lipase and pancreas lipase [93,180].Hodge and Smith (1964) reported fluoride at low concentrations (0.005 M ) is knownto inhibit lipase resulting in an accumulation of higher fatty acids [111].


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It is now accepted that an accumulation of fatty acids and obesity induce endoplasmicreticulum (ER) stress in liver, which suppresses insulin production and contributes todiabetes [181]. It is further known that fatty acids inhibit hormone-sensitive lipase(HSL) [182]. HSL is has important physiological functions affecting adipocytelipolysis, steroidogenesis, spermatogenesis, and perhaps insulin secretion and insulinaction [183]. Arner (1996) reported that increases in adipocyte lipolysis is a riskfactor in obesity and diabetes [184]. Miller and Auchus (2011) reported that alterationto steroidgenesis can contribute to disorders in reproduction, fertility, hypertension,obesity, and physiological homeostasis [185]. Chi et al (1998) reported thatabnormalities of phospholipids contribute to hypertension [186].

Importantly, the Food and Nutrition Board of the U.S National Research Council(1952) reported that minimum level of fluoride that produces certain toxic effects forlipase inhibition was 0.2ppm [187]. More recently Guan et al. (2000) showed that thesame concentration of fluoride that caused dental fluorosis affected kidney phospholipids [188].

This strongly indicates that the contribution of fluoride from artificial fluoridation tototal dietary exposure is contributing to chronic disease and physiological disorders.

10. Fluoride inhibits Calcium Homeostasis

There is no doubt that fluoride possesses the ability to complex calcium, therebyreducing its ionic concentrations [111]. The reduction in calcium ion concentration ofthe blood plasma and the body fluids could have a number of unfortunate physiological sequelae: muscle contraction is weakened; nerve conduction isdepressed,; blood clotting time may be greatly lengthened; cell membrane permeability may be drastically altered, thereby changing the entire pattern ofexchange of metabolites in the cell [111].

Fluoride is known to induce or exacerbate calcium deficiency by decreasing calciumabsorption in the gastro-intestinal tract, thus increasing the bodys calciumrequirements [11]. Vitamin D3 is one of the primary biological regulators of calciumhomeostasis [189], low calcium absorption has been linked to reduced vitamin D

status [190,191] and low vitamin D levels are associated with increased risk of asthmaand asthma morbidity[192]. The toxic effects of fluoride are more severe and complexin geographical areas with low calcium in drinking water and amongst individualswith dietary calcium deficiency. High risk subpopulation groups include growingchildren, adolescents, pregnant and lactating mothers, because of the greater demandsfor calcium [193-196].

It is not surprising therefore, that asthma is the most common chronic disease ofchildhood [197-200]. Prevalence rates have substantially increased in countries withartificial fluoridation, where the highest burdens of this disease are found globally at prevalence rates significantly above (hundreds of percent) those of other developed

countries [201-204]. Asthma has been also reported to affect 3.7 to 8.4 percent of pregnant women [205], making it potentially the most common serious medical


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problem to complicate pregnancy [206]. As noted previously fluoride exposure at biological relevant concentration has been found to elevate calcitonin in humans [11]and elevated calcitonin is an established risk factor in inflammatory lung disease [86].

It is further acknowledged that fluoride exposure can alter both thyroid and parathyroid function contributing to subclinical hypothyroidism, subclinicalhyperthyroidism and secondary hyperparathyroidism [11, 207]. Heaney (2003)reported that low calcium intake is associated with increased risk of osteoporosis,thyroid disorders, obesity, colon cancer and hypertension, [207].

It is estimated that 6.5% of the population in Ireland have osteoporosis [208],compared to 3.2% for the UK [209]. This represents 100% increased prevalence inthe RoI. As noted previously estimated prevalence of overweight in adults in the RoIis 37%, with 24% documented as obese [119]. According to the National CancerRegistry Ireland, the incidence of colon cancer in Ireland is higher than the Europeanaverage for both males and females [210]. In 2010, the Institute of Public Health(IPH) reported that more than 950,000 (62.2%) adults aged 45+ years in RoI havehypertension and more than 67,000 (3.7%) adults aged 18-44 years in RoI haveclinically diagnosed hypertension[211]. By 2020 the IPH report that the number ofadults aged 45+ years with hypertension is expected to rise to more than 1,220,000(63.1%)[211]. This represents a 28% increase (an additional 270,000 adults aged 45+years) in ten years. The differences in prevalence rates in the Island of Ireland areremarkable, with more than 75% of adults aged 65 years or over in the RoI clinicallydiagnosed with hypertension compared to 48% in non-fluoridated NorthernIreland[211].

11. Fluoride inhibits Magnesium Homeostasis

There is no doubt that fluoride possesses the ability to complex magnesium therebyreducing its ionic concentrations [111]. Magnesium is a required cofactor for over 300enzyme systems [212]. Fluoride forms magnesium-fluoride complexes that have aninhibitory effect on many enzymes. For example, Utter and Werkman (1942) foundthat the magnesium ion needed with enolase for converting 2-phosphoglyceric acid to phosphopyruvic acid was precipitated by fluoride as an insoluble fluoromagnesium- phosphor-protein complex [137]. Chamberlain and Burroughs (1962) reported thatlow levels of fluoride result in partial blocking of normal carbohydrate metabolismand that lower magnesium levels in the presence of fluoride significantly reduce

metabolic pathways of cellulose digestion. This inhibition was further increased whenlow levels of manganese are combined with low levels of magnesium [115].

Among its other effects, ingestion of fluoride increases the requirement for certainnutrients. For example, the metabolic requirement for magnesium is increased byfluoride, sequestering it into the skeleton and thereby making magnesium less biologically available [213]. There has been a gradual decline of dietary magnesiumin the developed economies in recent decades, largely due to increased consumptionof processed foods which are low in magnesium [214]. Magnesium deficiency is nowrelatively common in many developed countries such as the USA [215]. There arealso interactions between magnesium, calcium and vitamin D [215]. Duringmagnesium depletion, intracellular calcium rises. Since calcium plays an importantrole in skeletal and smooth muscle contraction, a state of magnesium depletion may


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חוות דעת ייצוגית declan waugh

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